Core Viewpoint - The in vivo CAR-T field has rapidly evolved over three years, marked by significant acquisitions and clinical advancements, culminating in major deals such as AbbVie’s $2.1 billion acquisition of Capstan Therapeutics and BMS’s $1.5 billion acquisition of Orbital Therapeutics [3][4]. Group 1: Acquisitions and Market Activity - AbbVie announced the acquisition of Capstan Therapeutics for $2.1 billion in cash, highlighting the growing interest in in vivo CAR-T therapies [3]. - BMS acquired Orbital Therapeutics for $1.5 billion, expanding its portfolio into the in vivo CAR-T cell therapy space [4]. - These acquisitions reflect a broader trend of increasing investment and collaboration in the CAR-T sector, indicating a robust market outlook [3][4]. Group 2: Technological Advancements - BMS's acquisition of Orbital enhances its cell therapy research platform, focusing on a potential best-in-class therapy aimed at autoimmune diseases [6]. - The therapy OTX-201, developed by Orbital, is in the pre-IND research stage and is expected to enter clinical trials in the first half of 2026 [6]. - OTX-201 utilizes optimized circular RNA (circRNA) to generate CAR-T cells in vivo, targeting CD19 to treat B-cell driven autoimmune diseases [7]. Group 3: Research and Development Focus - Orbital Therapeutics aims to develop next-generation RNA drugs that reprogram cells to treat diseases at their source, offering a simpler and safer alternative to current CAR-T therapies [10]. - The company’s platform integrates circRNA, linear RNA, targeted delivery systems, and AI-driven design to create durable and programmable therapies [10]. - In addition to autoimmune diseases, Orbital is also exploring in vivo CAR-T therapies for cancer and developing next-generation mRNA vaccines [12].

Core Insights - The article discusses the role of circular RNA (circRNA) in gene expression regulation, highlighting its importance in various biological processes and diseases, particularly cancer [2][8]. Group 1: CircRNA Mechanism and Function - Pre-mRNA reverse splicing leads to the production of circRNA, which shares nearly identical sequences with linear RNA but differs at the back-splicing junction (BSJ) [2]. - CircRNA plays significant roles in gene expression regulation, including transcription modulation, mRNA splicing interference, acting as "sponges" for miRNA or proteins, influencing translation, and even being translated into peptides [2]. - High-expression circRNA has been linked to maintaining quiescent hematopoietic stem cells, regulating cell growth and cancer progression, affecting brain function and neuronal development, and modulating innate immune responses [2]. Group 2: Research Findings on circMAN1A2 - A study published by Fudan University identified a circRNA, circMAN1A2(2,3,4,5), that is highly expressed in tumors and regulates colorectal cancer (CRC) development through RNA-RNA interactions [3][5]. - The research team analyzed the variable circularization (AC) patterns across multiple cell lines and CRC tissues, identifying the primary expressed circRNA at each AC gene locus [5]. - CircMAN1A2(2,3,4,5) enhances the stability of CENPB mRNA by interacting with its 3' untranslated region (3' UTR), and inhibiting this interaction can suppress CRC progression [7][8].